Interactions of rationally designed small peptide dendrons functionalized with valine or sinapic acid with α-helix and β-sheet structures of poly-l-lysine and poly-l-glutamic acid

Uncontrolled protein oligomerization leading to deposition of fibrils is related to several diseases including neurodegeneration and diabetes. Involvement of natural compounds in regulation of this process has been documented. Therefore, the design and detailed study of bioinspired new molecular entities is one of the possible avenues to achieve better therapeutics. Here, we provide experimental data derived from the application of chiraloptic methods that rationally designed, bioinspired small branched peptides influenced the primary conformation of both poly-l-lysine (PLL) and poly-l-glutamic acid (PLGA) polypeptides in a structure- and concentration-dependent manner. In several cases, the circular dichroism (CD) spectra of polypeptide/dendron mixtures were considerably different from those corresponding to the individual polypeptides, in terms of significant reduction of intensity, discrete structure, and dislocation of characteristic bands. Data deconvolution suggested that compared to the individual homo-polypeptides, the resulting polypeptide/dendron complexes had a relative gain of distorted alpha-helix, and right- and left-hand twisted beta-sheet forms, which may indicate a more diffuse structure. The electrostatic attraction and multiple hydrogen bonding between oppositely charged molecules, that is, between cationic-branched peptides and the beta-sheet surface formed by anionic PLGA, might be the main cause of coaggregation that increased the variety and contribution of less ordered forms, and reduced the propensity for self-aggregation.